Our objective is to determine why some breast cancer cells are responsive to hormones and endocrine therapy and others are not. We are using cloned lines of MCF-7, human breast carcinoma cells, which are dependent upon estrogen for growth as tumors in athymic mice, to determine the attributes of the implantation site and the malignant cell that determine hormone responsiveness and the effects of chemotherapy on that responsiveness. Our experimental approach combines cell culture and tumor histogenesis in athymic mice where quantitative data on cell response to hormone and their antagonists are applied in an attempt to modulate tumor growth in vivo.